In these studies, the dynamic relations between the factors which influence hepatic glucose production are being examined. Utilizing the isolated puppy liver, cross-perfused with whole blood, it has been shown that although the portal vein glucose level is the most important stimulus to glucose uptake, insulin exerts an important effect in determining the sensitivity of the uptake process to glucose. We are continuing these investigations to observe the dynamic relations between glucagon and insulin administered at doses within the physiological range as they affect glucose production. By utilizing a computer model of hepatic glucose metabolism, the hormonal effects can be interpreted in mechanistic terms. Finally, studies are being instituted to determine whether a reflex exists wherein the central nervous system regulates hepatic glucose production via direct neural pathways. BIBLIOGRAPHIC REFERENCES: El Refai, M. and R. N. Bergman. Further studies of a model of glycogen metabolism: interaction of insulin and glucose. Proc. Fifth Annual Meeting, Biomedical Engineering Society, April, 1975 (Abstract); Taborsky, G. J. and R. N. Bergman. The role of hypothalamic receptors in the control of free fatty acid and insulin release. The Physiologist (Aug., 1975).